The present invention relates generally to a process for making an emulsion, and more particularly to a process for making a sterile emulsion which employs an improved homogenizer having a piston configured to maintain the sterility of the emulsion during production. The present invention further relates to an improved valve block having a movable valve plunger, the valve block configured to maintain the sterility of an emulsion produced thereby.
Various techniques have been developed for the production of sterile therapeutic compounds and the like, including solutions, emulsions, and other liquids. Such techniques include sterile filtration and heat-processing. While these techniques are in widespread practice, they are not suitable for the production of all types of compounds. Experience has shown that for production of certain sterile emulsions, sterile filtration may not be effective in obtaining the desired level of sterility, while heat processing is unsuitable for certain heat-labile compounds.
The production of emulsions typically entails the use of a homogenizer which effects particle or globule size reduction in a mixture of two immiscible liquids. Such particle size reduction is effected by pressurization of a mixture to relatively high pressures, e.g., 7,000-20,000 psi, or more, followed by direction of the pressurized mixture through a valve assembly defining an appropriately sized orifice by which the mixture is accelerated to high velocities for impingement upon a particle-reducing surface, sometimes referred to as an impact ring. Operation of such homogenizers effects the desired particle size reduction for emulsion production.
A typical homogenizer includes one or more reciprocably operated pump pistons which act to pressurize the mixture of components from which the emulsion is formed. Such an apparatus also typically includes a valve assembly, including a valve plunger which can be adjusted for controlling the size of an orifice through which the pressurized mixture is directed. O-rings of known construction are used in connection with the pump pistons and valve plungers in order to seal the interior fluid pathway of the homogenizer from an external environment thereof.
Steam sterilization (xe2x80x9cSIPxe2x80x9d, i.e., steam in place) has been shown to be an effective method for sterilizing the fluid pathway defined by the homogenizer. Steam sterilization also effectively sterilizes those portions of the pump piston and adjustable valve plunger that are exposed to the steam. However, by virtue of the configuration of the typical homogenizer, a portion of the reciprocating pump piston, as well as a portion of the adjustable valve plunger, move between positions that are internal and external to the fluid pathway, i.e., between sterile and non-sterile environments. As a consequence, reciprocation of the pump piston, or adjustment of the valve plunger, can result in microbial ingress into the fluid pathway, potentially adversely affecting sterility of the emulsion being produced by the homogenizer. While it is possible to operate a homogenizer apparatus in a xe2x80x9cclean roomxe2x80x9d environment and thereby obviate the potential for microbial ingress, such a solution is both costly and cumbersome.
The present invention is particularly directed to a process and apparatus for forming a sterile emulsion wherein portions of the apparatus which are movable into and out of the fluid pathway of the apparatus are independently sterilized.
The present invention is directed to a process and related apparatus for the production of a sterile emulsion. The apparatus of the present invention defines a fluid pathway and a pumping bore where the pumping bore is in fluid communication with the fluid pathway. A reciprocable member having a first portion and a second portion is mounted such that the first portion is in fluid communication with the fluid pathway and such that the second portion moves into and out of fluid communication with the fluid pathway. The apparatus defines a sterilant passage constructed to deliver sterilant to a portion of the pumping bore adjacent to the second portion of the reciprocable member. In one embodiment of the present invention, the apparatus includes a wall defining a chamber therein, the wall being constructed to seal the reciprocable member from an external environment of the wall. The chamber defined by the wall is in fluid communication with the pumping bore.
The present invention also is directed to a valve body that defines a bore in fluid communication with the fluid pathway of a homogenizer. A valve plunger having a first portion and a second portion is mounted such that the first portion is in fluid communication with the fluid pathway and such that the second portion can be moved into and out of fluid communication with the fluid pathway. The apparatus further includes an apparatus constructed to sterilize the second portion of the valve plunger, thereby preventing microbial ingress into the fluid pathway.
The present invention is further directed to a method for performing homogenization. The method includes the step of providing a homogenizing apparatus constructed in accordance with the present invention, as above-described. The method also includes the step of effecting sterilization of the second portion of the reciprocable member and the second portion of the movable member. The method further includes the step of directing one or more emulsion constituents into the fluid pathway defined by the homogenizing apparatus. Thereafter, the reciprocable member is reciprocated in order to effect homogenization under sterile conditions.
Other features and advantages of the present invention will become readily apparent from the following detailed description, the accompanying drawings, and the appended claims.